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Ciguatera fish poisoning (CFP) is a form of food poisoning caused by consumption of varieties of toxic ciguatera fish species from tropical and subtropical waters. In the present review, significant features and perspective of LC/MS methods for CTXs as confirmatory methods are reviewed on the discussion for one of the best LC/MS/MS method reported by Yogi in 2011. More practical approach on the basis of the previous method is proposed with a single LC/MS by using selected ion monitoring (SIM). High resolution mass spectrometry (HRMS) coupled with LC is also proven as a reliable approach for identification of CTX analogues even in the situation that analytical standards are not available.

Several marine microalgae produce dangerous toxins very damaging to human health, aquatic ecosystems and coastal resources. These Harmful Algal Blooms (HABs) in recent decades seem greatly increased regarding frequency, severity and biogeographical level, causing serious health risks as a consequence of the consumption of contaminated seafood. Toxins can cause various clinically described syndromes, characterised by a wide range of symptoms: amnesic (ASP), diarrhoetic (DSP), azaspirazid (AZP), neurotoxic (NSP) and paralytic (PSP) shellfish poisonings and ciguatera fish poisoning. The spread of HABs is probably a result of anthropogenic activities and climate change, that influence marine planktonic systems, including global warming, habitat modification, eutrophication and growth of exogenous species in response to human pressures. HABs are a worldwide matter that requests local solutions and international cooperation. This review supplies an overview of HAB phenomena, and, in particular, we describe the major consequences of HABs on human health.

In the last decade, several outbreaks of ciguatera fish poisoning (CFP) have been reported in the Canary Islands (central northeast Atlantic Ocean), confirming ciguatera as an emerging alimentary risk in this region. Five Gambierdiscus species, G. australes, G. excentricus, G. silvae, G. carolinianus and G. caribaeus, have been detected in macrophytes from this area and are known to produce the ciguatoxins (CTXs) that cause CFP. A characterization of the toxicity of these species is the first step in identifying locations in the Canary Islands at risk of CFP. Therefore, in this study the toxicity of 63 strains of these five Gambierdiscus species were analysed using the erythrocyte lysis assay to evaluate their maitotoxin (MTX) content. In addition, 20 of the strains were also analysed in a neuroblastoma Neuro-2a (N2a) cytotoxicity assay to determine their CTX-like toxicity. The results allowed the different species to be grouped according to their ratios of CTX-like and MTX-like toxicity. MTX-like toxicity was especially high in G. excentricus and G. australes but much lower in the other species and lowest in G. silvae. CTX-like toxicity was highest in G. excentricus, which produced the toxin in amounts ranging between 128.2 &plusmn, 25.68 and 510.6 &plusmn, 134.2 fg CTX1B equivalents (eq) cell&minus, 1 (mean &plusmn, SD). In the other species, CTX concentrations were as follows: G. carolinianus (100.84 &plusmn, 18.05 fg CTX1B eq cell&minus, 1), G. australes (31.1 &plusmn, 0.56 to 107.16 &plusmn, 21.88 fg CTX1B eq cell&minus, 1), G. silvae (12.19 &plusmn, 0.62 to 76.79 &plusmn, 4.97 fg CTX1B eq cell&minus, 1) and G. caribaeus (&lt, LOD to 90.37 &plusmn, 15.89 fg CTX1B eq cell&minus, 1). Unlike the similar CTX-like toxicity of G. australes and G. silvae strains from different locations, G. excentricus and G. caribaeus differed considerably according to the origin of the strain. These differences emphasise the importance of species identification to assess the regional risk of CFP.

Gambierdiscus and Fukuyoa species have been identified in Aotearoa/New Zealand’s coastal waters and G. polynesiensis, a known producer of ciguatoxins, has been isolated from Rangitāhua/Kermadec Islands (a New Zealand territory). The warming of the Tasman Sea and the waters around New Zealand’s northern subtropical coastline heighten the risk of Gambierdiscus proliferating in New Zealand. If this occurs, the risk of ciguatera fish poisoning due to consumption of locally caught fish will increase. Research, including the development and testing of sampling methods, molecular assays, and chemical and toxicity tests, will continue. Reliable monitoring strategies are important to manage and mitigate the risk posed by this emerging threat. The research approaches that have been made, many of which will continue, are summarised in this review.

International audience

The recent emergence of ciguatera in the eastern Atlantic, particularly in the Canary Islands (Spain) and Madeira (Portugal) prompted the development and implementation of liquid chromatography tandem-mass spectrometry (LC/MS-MS) methods for the detection of ciguatoxins in fish. The complexity of fish tissue matrices, low concentrations of ciguatoxins in hazardous fish, and the scarcity of ciguatoxin standards present challenging issues for successful implementation of routine ciguatoxin analysis. A laboratory reference material of Caribbean Ciguatoxin-1 (C-CTX1), which was previously confirmed in fish responsible for ciguatera outbreaks in the Canary Islands, was used to assess the toxin's stability under strongly acidic conditions and solvent systems commonly used in LC-MS/MS. It was observed that strongly acidic conditions caused the transformation of C-CTX1 to a C56 methoxy congener, C-CTX1-Me. C-CTX1 was structurally characterised by LC-MS/MS and fragmentation pathways are presented showing the same fragmentation pattern as C-CTX1-Me. These results suggest that the use of strongly acidic conditions during sample pretreatment for C-CTX analysis, might produce significant artefacts, and risks failing to detect the presence of C-CTX1.

Ciguatera fish poisoning (CFP) is one of the most devastating food-borne illnesses caused by fish consumption. Ciguatoxins (CTXs) are potent neurotoxins synthesized by the benthic microalgae Gambierdiscus spp. and Fukuyoa spp. that are transmitted to fish by grazing and predation. Despite the high incidence of CFP, affecting an estimated number of 50,000 persons per year in tropical and subtropical latitudes, the factors underlying CTXs occurrence are still not well understood. Toxin transfer and dynamics in fish and food-webs are complex. Feeding habits and metabolic pathways determine the toxin profile and toxicity of fish, and migratory species may transport and spread the hazard. Furthermore, CTX effect on fish may be a limiting factor for fish recruitment and toxin prevalence. Recently, new occurrences of Gambierdiscus spp. in temperate areas have been concomitant with the detection of toxic fish and CFP incidents in non-endemic areas. CFP cases in Europe have led to implementation of monitoring programs and fisheries restrictions with considerable impact on local economies. More than 400 species of fish can be vectors of CTXs, and most of them are high-valued commercial species. Thus, the risk uncertainty and the spread of Gambierdiscus have serious consequences for fisheries and food safety. Here, we present a critical review of CTXs impacts on fish, fisheries, and humans, based on the current knowledge on CFP incidence and CTXs prevalence in microalgae and fish. SNMB-INOV: Innovation for a more competitive shellfish sector Operational Program Mar 2020, Portugal 2020 project Cigua - Portuguese Foundation for Science and Technology (FCT) [PTDC/CTA-AMB/30557/2017] FEDEREuropean Commission FCTPortuguese Foundation for Science and TechnologyEuropean Commission [UID/Multi/04326/2019] info:eu-repo/semantics/publishedVersion

Globally, ciguatera fish poisoning (CFP) avoidance efforts rely primarily on local knowledge of the fish being consumed, its collection location, and association with illnesses. In 2016, several fish that appeared to be hybrids between a local commercially prized species, Ocyurus chrysurus, and a regionally prohibited species Lutjanus apodus (due to CFP concerns), were caught nearshore in United States Virgin Islands waters, leading to confusion regarding the safety of consuming the fish. The hybrid status of the fish was verified as O. chrysurus (male) × L. apodus (female) by comparing two sets of gene sequences (mitochondrial CO1 and nuclear S7). Using an in vitro mouse neuroblastoma (N2a) assay, one of the hybrid fish exhibited a composite cytotoxicity of 0.038 ppb Caribbean ciguatoxin-1 (C-CTX-1) equivalents (Eq.); a concentration below the US Food and Drug Administration (FDA) guidance level for safety in fish products for CFP (0.1 ppb C-CTX-1 Eq.) but approximately 2× above the maximum described in the commercially prized parent species (0.019 ppb C-CTX-1 Eq./g). C-CTX-1 was confirmed in the hybrid sample by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The second hybrid fish tested negative for CTXs. This research confirms hybridization between two species with contrasting commercial statuses, discusses CTX accumulation implications for hybridization, and provides a methodology for future studies into novel CFP vectors, with the goal of providing critical information for fishermen and consumers regarding CFP risk management.

Ciguatera Fish Poisoning is a worldwide concern caused by the consumption of fish contaminated with ciguatoxins not only in endemic regions in the Pacific Ocean or the Caribbean Sea but also in emerging areas of Macaronesia on the eastern Atlantic. The recent emergence of these toxins in other coastal areas worldwide, prompted the need for the characterization of the risk in these areas. This Ciguatera Fish Poisoning risk has been recently identified as a potential threat in subtropical areas of the Atlantic coast and scientific efforts are being focused in the identification and confirmation of the toxins involved in this potential risk. Neuroblastoma cell assay has been widely used for the evaluation of the toxicity in several marine biotoxin groups, and found to be a very useful tool for toxicity screening. LC-MS/MS has been also used for confirmatory purposes although the main limitation of the advances on LC-MS/MS development is due to commercial unavailability of reference materials and hampers method implementation and validation or even confirmation of the ciguatoxins (CTXs) responsible for the toxic profiles. While neuroblastoma cell assay (N2a) is typically used for toxicity screening as mentioned above, being necessary to confirm this N2a toxicity by LC-MS/MS, this study is designed using N2a as a tool to confirm the toxicity of the fractions obtained corresponding to potential CTXs analogues according to the analysis by LC-MS/MS. With this aim, an amberjack sample (Seriola fasciata) from Selvagen Islads (Portugal) and implicated in Ciguatera Fish Poisoning was analyzed by LC-MS/MS and Caribbean Ciguatoxins were found to be mainly responsible for the toxicity. N2a was used in this work as a tool to help in the confirmation of the toxicity of fractions obtained by HPLC. Caribbean Ciguatoxin-1 was found as the main analogue responsible for the N2a toxicity while three Caribbean Ciguatoxin-1 (C-CTX1) metabolites which contribute to the total toxicity were also identified. info:eu-repo/semantics/publishedVersion

A major challenge in the international fish trade remains to reliably discriminate hundreds of fish species from possible substitutes which are perhaps not recommended for consumption. Recurring instances of ciguatera fish poisoning in the EU were associated with the consumption of mislabeled imported tropical fishes, mostly the red snapper Lutjanus malabaricus. Because the underlying fish species substitutions were only brought to the public attention due to resulting severe disease symptoms of this foodborne illness, we suggested a significant dark figure of undetected species substitutions with associated health risks. For the first time, the species identity of 975 individual fish imported into the EU at Frankfurt Airport from various provenances was correlated with their potential risk to cause ciguatera intoxication over a three-year period. Based on DNA sequence analysis and supporting peer-review of specimen photographs an overall mislabeling rate of 31% was determined which varied massively between 0% and 100% across fish families. Even though the sampling was not strictly random, this suggests massive fish species substitutions already at early stages of the value chain in the EU and over long time periods. From a health risk perspective, the occurrence of ciguatera-prone species in the cohort of DNA-identified substituted fish was dramatically higher compared to the correctly labeled fish (46% vs. 17%). Since our sampling largely reflects standardized official import procedures on fish labeling, these numbers suggest that the import of mislabeled tropical fishes, in particular snappers (Lutjanidae) and groupers (Serranidae), poses an underestimated health risk for seafood consumers in Europe.

Graphical abstract, Highlights • P-CTX-1B in 84 Spanish Mackerel from NSW and QLD were quantified using LC–MS/MS. • Liver & flesh from 6 fish and liver from 4 other fish were positive for P-CTX-1B. • Liver had significantly higher concentration (∼6 times) of P-CTX-1B than flesh. • No relationship was observed between length/weight of fish & detection of P-CTX-1B., Ciguatera Fish Poisoning (CFP) is a tropical disease caused by the consumption of fish contaminated with ciguatoxins (CTXs). Currently, the only feasible prevention methods for CFP are to avoid the consumption of fish of certain species from some regions, avoid larger fish of certain species, or avoid all fish caught from specific regions. Here, we quantified levels of P-CTX-1B in Spanish Mackerel (Scomberomorus commerson), which is the main fish species that causes CFP in New South Wales and Queensland, Australia, using LC–MS detection against a toxin standard. We found detectable P-CTX-1B in both flesh and liver tissues in fish from New South Wales (n = 71, 1.4% prevalence rate, with a confidence interval of 1%–4%, and 7% prevalence, 1%–12%, in flesh and liver, respectively). In the small sample of fish from Queensland, there was a 46% prevalence (19–73%, n = 13). Toxin levels found were 0.13 μg kg−1 to

© 2016 Elsevier B.V. Ciguatera fish poisoning (CFP) has been reported for many years in Rarotonga, Cook Islands, and has had the world's highest reported incidence of this illness for the last 20 years. Following intensive sampling to understand the distribution of the causative organisms of CFP, an undescribed Gambierdiscus species was isolated from the Rarotongan lagoon. Gambierdiscus cheloniae sp. nov. has the common Gambierdiscus Kofoidian plate formula (except for a variability in the number of precingular plates in aberrant cells): Po, 3′, 6″ (7″), 6C?, 6 or 7S, 5′″, 1p and 2″″. The 2′ plate is hatchet shaped and the dorsal end of 1p is pointed and the relatively narrow 1p plate. Morphologically G. cheloniae is similar to the genetically closely related species G. pacificus, G. toxicus and G. belizeanus, although smaller (depth and length) than G. toxicus. The apical pore plate varies from those of G. belizeanus and G. pacificus, which are shorter and narrower, and from G. toxicus, which is larger. G. cheloniae also differs from G. pacificus in the shape of the 2′ plate. The description of this new species is supported by phylogenetic analyses using three different gene regions. G. cheloniae produced the putative maitotoxin-3 analogue, MTX-3, but neither maitotoxin or monitored ciguatoxin. Extracts of G. cheloniae were shown to be highly toxic to mice by intraperitoneal (i.p.) injection, although they were less toxic by gavage. It is possible that this species produces toxins other than putative MTX-3.

Ciguatera fish poisoning (ciguatera) is a common clinical syndrome in areas where there is dependence on tropical reef fish for food. A subset of patients develops recurrent and, in some instances, chronic symptoms, which may result in substantial disability. To identify possible biomarkers for recurrent/chronic disease, and to explore correlations with immune gene expression, peripheral blood leukocyte gene expression in 10 ciguatera patients (7 recurrent and 3 acute) from the U.S. Virgin Islands, and 5 unexposed Florida controls were evaluated. Significant differences in gene expression were noted when comparing ciguatera patients and controls; however, it was not possible to differentiate between patients with acute and recurrent disease, possibly due to the small sample sizes involved.

International audience; Ciguatera Fish Poisoning (CFP) is a foodborne disease classically related to the consumption of tropical coral reef fishes contaminated with ciguatoxins (CTXs), neurotoxins produced by dinoflagellates of the Gambierdiscus genus. Severe atypical ciguatera-like incidents involving giant,clams, a marine resource highly consumed in the South Pacific, are also frequently reported in many Pacific Islands Countries and Territories. The present study was designed to assess the ability of giant clams to accumulate CTXs in their tissues and highlight the potential health risks associated with their consumption. Since giant clams are likely to be exposed to both free-swimming Gambierdiscus cells and dissolved CTXs in natural environment, ex situ contamination experiments were conducted as follows: giant clams were exposed to live or lyzed cells of TB92, a highly toxic strain of G. polynesiensis containing 5.83 +/- 0.85 pg P-CTX-3C equiv. cell(-1) vs. HIT0, a weakly toxic strain of G. toxicus containing only (2.05 +/- 1.16) x 10(-3) pg P-CTX-3C equiv. cell-1, administered over a 48 h period at a concentration of 150 cells mL(-1). The presence of CTXs in giant clams tissues was further assessed using the mouse neuroblastoma cell-based assay (CBA-N2a). Results showed that giant clams exposed to either lyzed or live cells of TB92 were able to bioaccumulate CTXs at concentrations well above the safety limit recommended for human consumption, i.e. 3.28 +/- 137 and 2.92 +/- 1.03 ng P-CTX-3C equiv. g(-1) flesh (wet weight), respectively, which represented approximately 3% of the total toxin load administered to the animals. In contrast, giant clams exposed to live or lyzed cells of HIT0 were found to be free of toxins, suggesting that in the nature, the risk of contamination of these bivalves is established only in the presence of highly toxic blooms of Gambierdiscus. Liquid chromatography-mass spectrometry (LC-MS/MS) analyses confirmed CBA-N2a results and also revealed that P-CTX-3B was the major CTX congener retained in the tissues of giant clams fed with TB92 cells. To the best of our knowledge, this study is the first to provide evidence of the bioaccumulation of Gambierdiscus CTX.s in giant clams and confirms that these bivalve molluscs can actually constitute another pathway in ciguatera poisonings. While most monitoring programs currently focus on fish toxicity, these findings stress the importance of a concomitant surveillance of these marine invertebrates in applicable locations for an accurate assessment of ciguatera risk.

In this review, the main objective was to describe the characteristic features of fatal ciguatera fish poisoning and identify contributory factors, with a view to promote prevention and public education. Ciguatera-related deaths, although rare, have been reported from the Pacific, Caribbean, and Indian Ocean regions. The clinical features were generally dominated by convulsions and coma, with various focal neurological signs. Several contributory factors could be identified, including consumption of ciguatoxin (CTX)-rich fish parts (viscera and head) in larger amounts, the most ciguatoxic fish species (e.g., Gymnothorax flavimarginatus) and reef fish collected after storms and individuals' susceptibility. Mass ciguatera fish poisoning with mortalities also occurred when G. flavimarginatus and other ciguatoxic fish species were shared in gatherings and parties. The characteristic features of fatal ciguatera fish poisoning must be recognized early. The public should be repeatedly reminded to avoid eating the most ciguatoxic fish species and the CTX-rich parts of reef fish. To prevent mass poisoning in gatherings and parties, the most ciguatoxic fish species and potentially toxic fish species must be avoided. Particularly after hits by disastrous storms, it is important to monitor the toxicity of reef fish and the incidence rates of ciguatera.

Ciguatera fish poisoning (CFP) is currently the most common marine biotoxin food poisoning worldwide, associated with human consumption of circumtropical fish and marine invertebrates that are contaminated with ciguatoxins. Ciguatoxins are very potent sodium-channel activator neurotoxins, that pose risks to human health at very low concentrations (>0.01 ng per g of fish flesh in the case of the most potent Pacific ciguatoxin). Symptoms of CFP are nonspecific and intoxication in humans is often misdiagnosed. Presently, there is no medically approved treatment of ciguatera. Therefore, to mitigate the risks of CFP, reliable detection of ciguatoxins prior to consumption of fish tissue is acutely needed, which requires application of highly sensitive and quantitative analytical tests. During the last century a number of methods have been developed to identify and quantify the concentration of ciguatoxins, including in vivo animal assays, cell-based assays, receptor binding assays, antibody-based immunoassays, electrochemical methods, and analytical techniques based on coupling of liquid chromatography with mass spectrometry. Development of these methods, their various advantages and limitations, as well as future challenges are discussed in this review.

Between 2015 and 2017, the NSW Food Authority investigated 4 ciguatera fish poisoning incidents linked to fish caught in tropical Australian and international waters and imported to New South Wales. Three of the implicated fish were caught near the Capel Bank Seamount, part of the Lord Howe Island Seamount Chain off the coast of Queensland. The fourth incident, in 2017, involved a fish caught between Cooktown and Lizard island, also off the Queensland coast. Thirteen individuals were affected. Early identification of potential Ciguatera fish poisoning (CFP) cases can facilitate a faster incident response, patient diagnosis and treatment. While different fish species were involved, and the severity and duration of symptoms varied between individuals, 3 of the 4 incidents were distinguished by those affected having consumed a fish meal prepared with the head of the fish. Affected individuals also described a sensation of hot/cold temperature reversal or a painful ‘sharpness’ when in contact with or drinking cold water. This paper outlines a series of incidents where a case’s symptoms, which can vary substantially in conjunction with their previous exposure history, the type of fish consumed and how the fish was cooked, can be used to identify potential CFP cases and hence CFP risks that may need to be addressed. Keywords: Ciguatera fish poisoning, ciguatoxins, seafood borne illness, New South Wales, Australia, Pacific ciguatoxin 1-B (P-CTX-1B).

Ciguatoxins (CTXs), endemic from tropical and subtropical regions of the Pacific and Indian Ocean and the Caribbean Sea, have caused several human poisonings during the last decade in Europe. Ciguatera fish poisonings (CFP) in Madeira and Canary Islands appear to be particularly related with consumption of fish caught close to Selvagens Islands, a Portuguese natural reserve composed of three small islands that harbor high fish biomass. In this study, fish specimens considered as potential vectors of CTXs were caught in Madeira and Selvagens archipelagos for toxins determination via sensitive liquid chromatography with tandem mass spectrometry detection (LC&ndash, MS/MS). CTXs were found in most of the fish samples from Selvagens and none from Madeira. Caribbean ciguatoxin-1 (C-CTX1) was the only toxin congener determined, reaching the highest value of 0.25 &micro, g C-CTX1 kg&minus, 1 in a 4.6 kg island grouper (Mycteroperca fusca). This study indicates that a diversity of fish from different trophic levels contains CTXs, Selvagens appear to be one of the most favorable locations for CTXs food web transfer and finally, this study highlights the need of further research based on intensive environmental and biological sampling on these remote islands.

Synthesis of the LMN-ring fragment of Caribbean ciguatoxin C-CTX-1, the principal causative toxin for ciguatera fish poisoning around the Caribbean Sea areas, is described. The key feature of the synthesis is the stereoselective introduction of an angular methyl group on the sterically encumbered seven-membered M-ring by the application of a hydrogen atom transfer-based reductive olefin coupling.

Gambierdiscus spp. are the major culprit responsible for global ciguatera fish poisoning (CFP). At present, the effects of microbiological factors on algal proliferation and toxin production are poorly understood. To evaluate the regulatory roles of quorum-sensing (QS) bacteria in the physiology of Gambierdiscus, co-culture experiments with screened QS strains were conducted in this study. Except for the growth-inhibiting effect from the strain Marinobacter hydrocarbonoclasticus, the algal host generally displayed much higher growth potential and toxin production ability with the existence of QS strains. In addition, Bacillus anthracis particularly exhibited a broad-spectrum growth enhancement effect on various Gambierdiscus types, as well as a remarkable influence on algal toxicity. The variations of algal physiological status, including growth rate, chlorophyll content, and responsive behaviors, are potential reasons for the observed positive or negative affection. This study suggests that QS bacteria regulate the algal growth and toxin production. Based on the evidence, we further speculate that QS bacteria may contribute to the site-specific distribution of CFP risk through regulating the algal host biomass and toxicity.

Ciguatera fish poisoning (CFP) caused by the consumption of fish that have accumulated ciguatoxins (CTXs) affects more than 50000 people annually. The spread of CFP causes enormous damage to public health, fishery resources, and the economies of tropical and subtropical endemic regions. The difficulty in avoiding CFP arises from the lack of sensitive and reliable analytical methods for the detection and quantification of CTXs in contaminated fish, along with the normal appearance, smell, and taste of fish contaminated with the causative toxins. Thus, an accurate, sensitive, routine, and portable detection method for CTXs is urgently required. We have successfully developed a highly sensitive fluorescent sandwich ELISA, which can detect, differentiate, and quantify four major CTX congeners (CTX1B, CTX3C, 51-hydroxyCTX3C, and 54-deoxyCTX1B) with a detection limit of less than 1 pg/mL. The ELISA protocol, using one microtiter plate coated with two mAbs (10C9 and 3G8), and ALP-linked 8H4, can detect any of the four CTX congeners in a single operation. CTX1B spiked into fish at the FDA guidance level of 0.01 ppb CTX1B equivalent toxicity in fish from Pacific regions was also proven to be reliably detected by this ELISA. Furthermore, the efficiency of extraction/purification procedures and the matrix effect of contaminants in fish were evaluated in detail, since pretreatment and matrix effects are critical for ELISA analysis.

Historical records of ciguatera in Mexico date back to 1862. This review, including references and epidemiological reports, documents 464 cases during 25 events from 1984 to 2013: 240 (51.72%) in Baja California Sur, 163 (35.12%) in Quintana Roo, 45 (9.69%) in Yucatan, and 16 (3.44%) cases of Mexican tourists intoxicated in Cuba. Carnivorous fish, such as snapper (Lutjanus) and grouper (Epinephelus and Mycteroperca) in the Pacific Ocean, and great barracuda (Sphyraena barracuda) and snapper (Lutjanus) in the Atlantic (Gulf of Mexico and Caribbean Sea), were involved in all cases. In the Mexican Caribbean, a sub-record of ciguatera cases that occurred before 1984 exists. However, the number of intoxications has increased in recent years, and this food poisoning is poorly studied in the region. Current records suggest that ciguatera fish poisoning in humans is the second most prevalent form of seafood poisoning in Mexico, only exceeded by paralytic shellfish poisoning (505 cases, 21 fatalities in the same 34-year period). In this study, the status of ciguatera in Mexico (epidemiological and treatment), and the fish vectors are reviewed. Dinoflagellate species Gambierdiscus, Ostreopsis, and Prorocentrum are related with the reported outbreaks, marine toxins, ecological risk, and the potential toxicological impact.

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. Between 2014 and 2016, five cases of ciguatera fish poisoning (CFP), involving twenty four individuals, were linked to Spanish Mackerel (Scomberomorus commerson) caught in the coastal waters of the state of New South Wales (NSW) on the east coast of Australia. Previously, documented cases of CFP in NSW were few, and primarily linked to fish imported from other regions. Since 2015, thirteen individuals were affected across four additional CFP cases in NSW, linked to fish imported from tropical locations. The apparent increase in CFP in NSW from locally sourced catch, combined with the risk of CFP from imported fish, has highlighted several considerations that should be incorporated into risk management strategies to minimize CFP exposure for seafood consumers.

Two new compounds heliotropiumides A (1) and B (2), phenolamides each with an uncommon carbamoyl putrescine moiety, were isolated from the seeds of a naturalized Hawaiian higher plant, Heliotropium foertherianum Diane & Hilger in the borage family, which is widely used for the treatment of ciguatera fish poisoning. The structures of compounds 1 and 2 were characterized based on MS spectroscopic and NMR analysis, and DP4+ calculations. The absolute configuration (AC) of compound 1 was determined by comparison of its optical rotation with those reported in literature. Compound 2 showed inhibition against NF-κB with an IC50 value of 36 μM. Fil: Cai, You-Sheng. University of Hawaii at Hilo; Estados Unidos. Wuhan University; China Fil: Sarotti, Ariel Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Gündisch, Daniela. University of Hawaii at Hilo; Estados Unidos Fil: Kondratyuk, Tamara P.. University of Hawaii at Hilo; Estados Unidos Fil: Pezzuto, John. Long Island University; Estados Unidos. University of Hawaii Cancer Center; Estados Unidos Fil: Turkson, James. University of Hawaii Cancer Center; Estados Unidos Fil: Cao, Shugeng. University of Hawaii at Hilo; Estados Unidos

© 2017 by the authors. Licensee MDPI. Ciguatoxins (CTXs), and possibly maitotoxins (MTXs), are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean). The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia), 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS), and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae, G. pacificus, G. honu, and F. paulensis) contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration.

Maitotoxin (MTX) is the most potent marine toxin known to date. It is responsible for a particular human intoxication syndrome called ciguatera fish poisoning (CFP). Several reports indicate that MTX is an activator of non-selective cation channels (NSCC) in different cell types. The molecular identity of these channels is still an unresolved topic, and it has been proposed that the transient receptor potential (TRP) channels are involved in this effect. In Xenopus laevis oocytes, MTX at picomolar (pM) concentrations induces the activation of NSCC with functional and pharmacological properties that resemble the activity of TRP channels. The purpose of this study was to characterize the molecular identity of the TRP channel involved in the MTX response, using the small interference RNA (siRNA) approach and the two-electrode voltage-clamp technique (TEVC). The injection of a specifically designed siRNA to silence the transient receptor potential canonical type 1 (TRPC1) protein expression abolished the MTX response. MTX had no effect on oocytes, even at doses 20-fold higher compared to cells without injection. Total mRNA and protein levels of TRPC1 were notably diminished. The TRPC4 siRNA did not change the MTX effect, even though it was important to note that the protein level was reduced by the silencing of TRPC4. Our results suggest that MTX could be a selective activator of TRPC1 channels in X. laevis oocytes and a useful pharmacological tool for further studies on these TRP channels.

Friedman, Melissa A. ... et al.-- 41 pages, 6 tables, 2 boxes, Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or months. This paper is a general review of CFP including the human health effects of exposure to ciguatoxins (CTXs), diagnosis, human pathophysiology of CFP, treatment, detection of CTXs in fish, epidemiology of the illness, global dimensions, prevention, future directions, and recommendations for clinicians and patients. It updates and expands upon the previous review of CFP published by Friedman et al. (2008) and addresses new insights and relevant emerging global themes such as climate and environmental change, international market issues, and socioeconomic impacts of CFP. It also provides a proposed universal case definition for CFP designed to account for the variability in symptom presentation across different geographic regions. Information that is important but unchanged since the previous review has been reiterated. This article is intended for a broad audience, including resource and fishery managers, commercial and recreational fishers, public health officials, medical professionals, and other interested parties, This work was funded in part by the National Institutes of Health (NIH) training grant at University of Southern California (T32 ES013678) and by an NIH center grant at Emory University (P30 ES019776). Funding was also provided by The National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Environmental Change and Health at the London School of Hygiene and Tropical Medicine in partnership with Public Health England (PHE), and in collaboration with the University of Exeter, University College London, and the Met Office; the UK Medical Research Council and the UK Natural Environment Research Council (NERC). In addition, this study contributes to the implementation of the objectives of the GlobalHAB project, supported by NSF grant OCE-1243377 to SCOR, and by the IOC/UNESCO, We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

Summary The benthic dinoflagellates in the genus Gambierdiscus produce toxins that bioaccumulate in tropical and sub-tropical fish causing ciguatera fish poisoning (CFP). Other co-occurring genera such as Coolia have also been implicated in causing CFP. Little is known about the diversity of the two genera Gambierdiscus and Coolia along the Thai coasts. The results of morphological analyses based on observation under light microscopy and scanning electron microcopy showed that strains of Gambierdiscus from Thailand displayed the typical Gambierdiscus plate formula: Po, 4′, 0a, 6″, 6c,?s, 5′′′, 0p and 2′′′′. Morphological examination of Thai Gambierdiscus enabled it to be identified as Gambierdiscus caribaeus: round and anterior-posteriorly compressed cell shape, broad 2′′′′ plate, rectangular 2′ plate, and symmetrical 3″ plate. The phylogenetic analyses based on the large subunit (LSU) rDNA D8/D10 sequences of Gambierdiscus from Thailand confirmed the morphological identification. The thecal plate formula for all of the Coolia isolates from Thailand was Po, 4′, 0a, 6″,?c,?s, 5′′′, 0p and 2′′′′. Most, but not all, of these isolates could be identified morphologically as Coolia malayensis. An LSU rDNA D1/D2 phylogenetic analysis confirmed identity of C. malayensis isolates identified morphologically. The remaining unidentified isolates fell in the C. tropicalis clade.

The isolation and culturing of toxic Gambierdiscus species is desirable for obtaining reliable sources of toxins responsible for Ciguatera Fish Poisoning (CFP) in order to provide reference materials and purified standards for chemical analyses and bioassays. Gambierdiscus polynesiensis CAWD212, G. pacificus CAWD213 and G. australes CAWD149 and 216 have been isolated from samples of sea water from the Cook Islands. G. polynesiensis produced ciguatoxins (CTX; 18.2 pg per cell) and G. australes CAWD149 produced maitotoxin (MTX; 8.3 pg per cell) and in both extracts putative MTX-3 was detected. G. pacificus also produced putative MTX-3. The toxicities of extracts of G. polynesiensis and G. pacificus were similar by i.p. injection (LD50s of 1.0 mg/kg and 0.8 mg/kg respectively), but when administered by gavage, the MTX-3 analogue producing G. pacificus (LD50 251 mg/kg) was 30-times less toxic than the CTX-producing G. polynesiensis (LD50 7.9 mg/kg). Consumption of fish contaminated by CFP has caused illness and even death in the Cook Islands and throughout the Pacific region and is now considered a globally neglected disease. Large-scale cultures of these organisms are now available, and isolation of the toxins they produce is in progress.

Ciguatera, an ichtyosarcotoxism linked to the consumption of usually healthy coral fish is a common poisoning in the Pacific, Caribbean and Indian Ocean where it is endemic. However, increased tourism and commercial transportation of tropical fish for consumption make it an unexceptional intoxication in countries away from its endemic area. Environmental stresses such as climate changes also contribute to the expansion of its geographical area. The non-specific clinical symptomatology is characterized by the occurrence of gastrointestinal, cardiovascular, nervous and general signs few hours after eating a ciguatoxic fish. The diagnosis is clinical and relatively easy in endemic areas but much less for physicians who are rarely confronted with, which is a source of prolonged diagnostic delays and a significant increase in spending. Treatment of ciguatera is symptomatic but new treatments, still experimental, give a real hope for the future.

Background: Warm sea surface temperatures (SSTs) are positively related to incidence of ciguatera fish poisoning (CFP). Increased severe storm frequency may create more habitat for ciguatoxic organisms. Although climate change could expand the endemic range of CFP, the relationship between CFP incidence and specific environmental conditions is unknown. Objectives: We estimated associations between monthly CFP incidence in the contiguous United States and SST and storm frequency in the Caribbean basin. Methods: We obtained information on 1,102 CFP-related calls to U.S. poison control centers during 2001–2011 from the National Poison Data System. We performed a time-series analysis using Poisson regression to relate monthly CFP call incidence to SST and tropical storms. We investigated associations across a range of plausible lag structures. Results: Results showed associations between monthly CFP calls and both warmer SSTs and increased tropical storm frequency. The SST variable with the strongest association linked current monthly CFP calls to the peak August SST of the previous year. The lag period with the strongest association for storms was 18 months. If climate change increases SST in the Caribbean 2.5–3.5°C over the coming century as projected, this model implies that CFP incidence in the United States is likely to increase 200–400%. Conclusions: Using CFP calls as a marker of CFP incidence, these results clarify associations between climate variability and CFP incidence and suggest that, all other things equal, climate change could increase the burden of CFP. These findings have implications for disease prediction, surveillance, and public health preparedness for climate change. Citation: Gingold DB, Strickland MJ, Hess JJ. 2014. Ciguatera fish poisoning and climate change: analysis of National Poison Center data in the United States, 2001–2011. Environ Health Perspect 122:580–586; http://dx.doi.org/10.1289/ehp.1307196

Prorocentrum lima is one of the microalgae species in Dinoflagellates group, which could cause Ciguatera Fish Poisoning (CFP) syndrome. P. lima commonly found it attached to various kind of macroalgae species and could cause human poisoning through biomagnification process in the food chain. Research on the abundance of P. lima and the environmental factors influences had been conducted in Karimunjawa Island, on 24 August 2018, and the objective of the research is to analyze the P. lima distributions in Karimunjawa waters, based on the cells abundance and environmental factors. The research was carried out by collecting macroalgae Padina and Sargassum at four stations, in the reef flat of Karimunjawa Island. Macroalgae were put inside plastic bottles and vigorously shaken by vortex (12500 rpm, 1 minute). Water samples separated from the macroalgae, filtered through a series of sieves, and then observed under a light microscope. The environmental factors are analyzed by Principal Component Analysis (PCA). Results showed a high abundance of P. lima found at Station 1 (Tanjung Gelam beach), which are 266 cells/ml on Padina and 210 cells/ml on Sargassum. Based on PCA analysis, Station 1 was characterized by water current, light intensity, phosphate, and depth. Those environmental factors should support the higher abundance of P. lima cells at the station.

Ciguatera fish poisoning is the most common marine food poisoning worldwide. It has been hypothesized that increasing seawater temperature will result in increasing ciguatera incidence. In St. Thomas, US Virgin Islands, we performed an island-wide telephone survey (N = 807) and a medical record review of diagnosed ciguatera cases at the emergency department of the sole hospital and compared these data with comparable data sources collected in 1980. Annual incidence from both recent data sources remained high (12 per 1,000 among adults in the telephone survey). However, the combined data sources suggest that incidence has declined by 20% or more or remained stable over 30 years, whereas seawater temperatures were increasing. Illness was associated with lower education levels, higher levels of fish consumption, and having previous episodes of ciguatera; population shifts from 1980 to 2010 in these factors could explain an incidence decline of approximately 3 per 1,000, obscuring effects from rising seawater temperature.

A previously healthy 39-year-old Canadian-born man travelled to Havana, Cuba, for one week on business. He stayed in a local home and ate foods prepared by the family. The night before his departure home, he ate two portions of a large fish identified by the host as a dog snapper ([Figure 1][1]).

Marine biotoxins are natural toxins produced by specific algae species. These toxins can accumulate in seafood such as mussels, oysters and fish. Consumption of contaminated seafood may lead to severe intoxication such as memory loss, paralysis, diarrhoea and even death. In order to protect consumers, a wide variety of methods have been developed. Historically, methods were based on in vivo animal assays. Alternatives for these animal unfriendly and unethical assays have been developed and are still under development. Other alternative methods are based on in vitro cell assays, receptor binding assays, immunological assays and analytical chemical techniques. This chapter gives an overview on the available methodologies and their application for the determination of marine biotoxins in seafood.

Ciguatera fish poisoning is the most frequently reported seafood toxin illness associated with the ingestion of contaminated tropical fish. Diagnosis relies on a history of recent tropical fish ingestion and subsequent development of gastrointestinal, cardiovascular, and neurological symptoms. Ciguatera poisoning usually has a self-limited time course, and its management involves symptomatic control and supportive care. This case report presents an uncommon case of ciguatera poisoning with prolonged intractable seizures refractory to standard antiseizure medications. The patient also had significant functional decline that responded to rigorous inpatient rehabilitation not previously described in literature.

The benthic dinoflagellate Gambierdiscus produces ciguatoxins (CTXs) and maitotoxins (MTXs), the most potent marine toxins known to date. CTXs bio-accumulate and cause Ciguatera Fish Poisoning (CFP). Recently, an increasing number of species has been discovered in this genus, and CFP has been reported from areas previously not considered endemic, namely the Canary Islands. Little is known about CTX and MTX congeners produced by microalgae, especially by strains outside the Pacific Ocean. Moreover, other toxic compounds were recently identified, e.g. gambierone. For isolation purposes, it is necessary to up-scale laboratory cultures of Gambierdiscus and develop a purification procedure capable of detecting previously undescribed compounds. Several strains of Gambierdiscus from the Pacific and North-Eastern Atlantic Oceans were screened for their toxicity using an ouabain/veratridine neuro-2a (N2a) assay and a human erythrocyte lysis assay (ELA). One strain from the Canary Islands showed particularly high toxicity but did not contain known ciguatoxins. For selected strains, algal cells were extracted with methanol. Crude extracts were partitioned between dichloromethane (DCM) and aqueous methanol (aq. MeOH) in order to separate lipophilic compounds (e.g. CTXs) from hydrophilic and amphiphilic compounds such as MTXs. Extracts were purified via successive fractionation steps, using different separation principles such as size exclusion and polarity. For each step of the purification, fractions were screened in parallel for toxicity using in vitro functional assays and analyzed by high resolution mass spectrometry (Q-Tof 6550, Agilent). Data-mining was carried out to establish molecular networks in highly toxic, purified fractions and to correlate such networks to toxicity.